10°C vs 4°C Lung Preservation RCT

• ClinicalTrials.gov Identifier: NCT05898776
• Recruitment Status: Recruiting
• First Posted: June 12, 2023
• Last Update Posted: April 12, 2024
• Sponsor: University Health Network, Toronto
• Collaborators: Medical University of Vienna; Vanderbilt University; Puerta de Hierro Majadahonda University Hospital; University of California, San Francisco
• Information provided by (Responsible Party): University Health Network, Toronto

Tracking Information

• First Submitted Date: May 31, 2023
• First Posted Date: June 12, 2023
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: June 9, 2023
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 9, 2023)

Incidence of Primary Graft Dysfunction (PGD) Grade 3 as per International Society for Heart and Lung Transplantation (ISHLT) [ Time Frame: 72 hours post-transplant ]

PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 9, 2023)

• Incidence of Primary Graft Dysfunction Grade 2-3 as per International Society for Heart and Lung Transplantation [ Time Frame: 0 (ICU arrival), 24, 48, and 72 hours post-transplant ]
  PGD is graded on a scale of 0 to 3 based on ISHLT guidelines, where PGD Grade 3 indicates severe primary graft dysfunction.
• Time on ventilator [ Time Frame: Index hospitalization (up to 1 year) ]
• Total ICU and hospital length of stay [ Time Frame: Index hospitalization (up to 1 year) ]
• Overall survival [ Time Frame: 30 days, 1 year post-transplant ]
• Occurrence of acute rejection [ Time Frame: 1 year post-transplant ]
• Six minute walk test [ Time Frame: 1 year post-transplant ]
• Forced expiratory volume - one second (FEV1 in L) [ Time Frame: 1 year post-transplant ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 10°C vs 4°C Lung Preservation RCT
• Official Title: Safety of 10°C Lung Preservation vs. Standard of Care: A Multi-Centre Prospective Non-Inferiority Trial

Brief Summary

Despite lung transplantation (LTx) being the most effective treatment for end-stage lung disease, its success rate is lower than that of other solid organ transplantations. Primary graft dysfunction (PGD) is the most common post-operative complication and a major factor in early mortality and morbidity, affecting ~25% of lung transplant patients. Induced by ischemia reperfusion, PGD represents a severe and acute lung injury that occurs within the first 72 hours after transplantation, and has a significant impact on short- and long-term outcomes, and a significant increase in treatment costs. Any intervention that reduces the risk of PGD will lead to major improvements in short- and long-term transplant outcomes and health care systems.

One of the main strategies to reduce the risk and severity of post-transplant PGD is to improve pre-transplant donor lung preservation methods. In current practice, lung preservation is typically performed by cold flushing the organ with a specialized preservation solution, followed by subsequent hypothermic storage on ice (~4°C). This method continues to be used and applied across different organ systems due to its simplicity and low cost. Using this method for the preservation of donor lungs, the current maximum accepted preservation times have been limited to approximately 6-8h. While the goal of hypothermic storage is to sustain cellular viability during ischemic time through reduced cellular metabolism, lower organ temperature has also been shown to progressively favor mitochondrial dysfunction. Therefore, the ideal temperature for donor organ preservation remains to be defined and should maintain a balance between avoidance of mitochondrial dysfunction and prevention of cellular exhaustion. In addition to that, safe and longer preservation times can lead to multiple advantages such as moving overnight transplants to daytime, more flexibility to transplant logistics, more time for proper donor to recipient matching etc.

Building on pre-clinical research suggesting that 10°C may be the optimal lung storage temperature, a prospective, multi-center, non-randomized clinical trial was conducted at University Health Network, Medical University of Vienna and Puerta de Hierro Majadahonda University Hospital. Donor lungs meeting criteria for direct transplantation and with cross clamp times between 6:00pm - 4:00am were intentionally delayed to an earliest allowed start time of 6:00am and a maximum preservation time from donor cold flush to recipient anesthesia start time of 12 hours. Lungs were retrieved and transported in the usual fashion using a cooler with ice and transferred to a 10°C temperature-controlled cooler upon arrival to transplant hospital until implantation. The primary outcome of this study was incidence of Primary Graft Dysfunction (PGD) Grade 3 at 72h, with secondary endpoints including: recipient time on the ventilator, ICU Length of Stay (LOS), hospital LOS, 30-day survival and lung function at 1-year. Outcomes were compared to a contemporaneous conventionally transplanted recipient cohort using propensity score matching at a 1:2 ratio. 70 patients were included in the study arm. Post-transplant outcomes were comparable between the two groups for up to 1 year. Thus, intentional prolongation of donor lung preservation at 10°C was shown to be clinically safe and feasible.

In the current study design, the investigators will conduct a multi-centre, non-inferiority, randomized, controlled trial of 300 participants to compare donor lung preservation from the time of explant to implant at ~10°C in X°Port Lung Transport Device (Traferox Technologies Inc.) vs a standard ice cooler. When eligible donor lungs become available for a consented recipient, the lungs will be randomized to undergo a preservation protocol using either 10°C (X°Port Lung Transport Device, Traferox Technologies Inc.) or standard of care. The primary outcome of the study is incidence of ISHLT Primary Graft Dysfunction Grade 3 at 72 hours. Post-transplant outcomes will be followed for one year.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Lung Transplant
• Organ Preservation

Intervention

• Device: Lung transplantation after 10°C donor lung preservation
  When suitable donor lungs become available for a, eligible, consented recipient and meet criteria to go straight to transplantation, the lungs randomized to 10°C preservation will be stored, transported and preserved in the X°Port Lung Transport Device (Traferox Technologies Inc.) until implant with a maximum time of 12 hours between the donor and recipient surgeries.
• Device: Lung transplantation after standard ice cooler donor lung preservation
  When suitable donor lungs become available for a, eligible, consented recipient and meet criteria to go straight to transplantation, the lungs randomized to standard preservation will be will be stored, transported and preserved in an ice cooler (~4°C, standard of care) until implant with a maximum time of 6 hours between the donor and recipient surgeries.

Study Arms

• Experimental: 10°C lung preservation
  Intervention: Device: Lung transplantation after 10°C donor lung preservation
• Active Comparator: Standard lung preservation
  Intervention: Device: Lung transplantation after standard ice cooler donor lung preservation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 9, 2023): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2026
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Donor Inclusion Criteria

• Donation after brain death (DBD) or donation after cardiac death (DCD)
• Donor lungs are suitable to go straight to LTx (i.e., do not need ex vivo lung perfusion (EVLP) assessment)

Donor Exclusion Criteria

• Concerns with organ preservation technique
• Need for EVLP assessment

Recipient Inclusion Criteria

• 18-80 years old
• Primary lung transplantation
• Bilateral lung transplantation

Recipient Exclusion Criteria

• Re-transplantation
• Multi-organ transplantation
• Single lung transplantation
• Participation in a contraindicating trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sharaniyaa Balachandran; 416-340-4800 ext 6549; sharaniyaa.balachandran@uhn.ca

• Listed Location Countries: Austria, Canada, Spain, United States

Administrative Information

• NCT Number: NCT05898776
• Other Study ID Numbers: 22-5909
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Health Network, Toronto
• Original Responsible Party: Same as current
• Current Study Sponsor: University Health Network, Toronto
• Original Study Sponsor: Same as current

Collaborators

• Medical University of Vienna
• Vanderbilt University
• Puerta de Hierro Majadahonda University Hospital
• University of California, San Francisco

Investigators

• Principal Investigator: Elliot Wakeam, MD MPH; University Health Network, Toronto

• PRS Account: University Health Network, Toronto
• Verification Date: April 2024